DNA Triplex and Quadruplex Assembled Nanosensors for Correlating K⁺ and pH in Lysosomes

It remains an unanswered question whether the flux of K⁺ and H⁺ in lysosomes are correlated due to difficulties in simultaneously imaging these two ions. This question is of great value for understanding lysosomal acidification. Herein, we designed DNA quadruplex and triplex based luminescent nanosensors that can, respectively monitor K⁺ and pH in lysosomal lumen. Each sensor contained an upconversion nanoparticle luminophore and a gold nanoparticle quencher, producing green and blue luminescence signals for K⁺ and H⁺, respectively. The sensors were tested in buffers showing dynamic ranges of 5 to 200 mM K⁺ and pH 5.0 to 8.2. Co-imaging using these two sensors in cells indicated that the influx of H⁺ was accompanied with the efflux of K⁺, solving this long-standing question of the lysosomal biochemistry.